Gastric cancer incidence overall has declined in the U.S. during the past 50 years but the incidence of adenocarcinoma of the gastric cardia and lower esophagus has recently substantially increased. Compared to gastric and esophageal cancer overall, adenocarcinoma of the gastric cardia and lower esophagus is characterized by a high male to female ratio and is relatively more common in whites. Experimental and clinical evidence suggest that duodenal gastric or esophageal reflux may play an etiologic role in proximal gastric carcinogenesis. Histamine2 (H2)-receptor antagonists (H2-blockers) were introduced in the mid-1970s and have become the treatment of choice for peptic ulcer disease and gastroesophageal reflux disorders. H2-blockers are potentially involved in gastric carcinogenesis. These drugs alter gastric acid production, increasing gastric pH and allowing reflux of alkaline duodenal refluxate into the proximal stomach and lower esophagus. Furthermore these drugs can be nitrosated to form mutagenic N-nitroso compounds. We propose a population-based case-control study to evaluate the role of this category of drugs (including possible effects of age at first use, dose, duration of use, latency and condition for which H2-blockers were prescribed) as well as other possible risk factors (e.g., use of other categories of drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, prior benign conditions of the stomach and esophagus, smoking and alcohol use, dietary factors, and Helicobacter pylori infection) in the etiology of adenocarcinoma of the gastric cardia/lower esophagus. Cases will be identified by the population-based Cancer Surveillance Program Core Resource over 4.5 years. Controls will be neighborhood controls matched 2:1 with cases on age, race, and sex. A total of 410 case-control triplets will be interviewed during the course of this study.